Analogues of 1-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo-[5,6]-cyclohepta [1,2-b]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase

Bioorg Med Chem. 1999 Sep;7(9):1845-55. doi: 10.1016/s0968-0896(99)00103-0.

Abstract

The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]-pyridin-11-yl)pi perazine/piperidine 3 is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds 7a-7g led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues 7i, 13i, and 13j. The 11R(-) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Pyridines / chemistry*
  • Pyridines / pharmacology
  • Spectrum Analysis
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Piperidines
  • Pyridines
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase